Abstract
Determinants of growth and metastasis in cancer remain of great interest to define. MicroRNAs (miRNAs) have frequently emerged as tumor metastatic regulator by acting on multiple signaling pathways. Here we report the definition of miR-346 as a novel oncogenic microRNA that facilitates non-small cell lung cancer (NSCLC) cell growth and metastasis. XPC, an important DNA damage recognition factor in nucleotide excision repair was defined as a target for down-regulation by miR-346, functioning through direct interaction with the 3′-UTR of XPC mRNA. Blocking miR-346 by an antagomiR was sufficient to inhibit NSCLC cell growth and metastasis, an effect that could be phenol-copied by RNAi-mediated silencing of XPC. In vivo studies established that miR-346 overexpression was sufficient to promote tumor growth by A549 cells in xenografts mice, relative to control cells. Overall, our results defined miR-346 as an oncogenic miRNA in NSCLC, the levels of which contributed to tumor growth and invasive aggressiveness.
Highlights
Lung cancer remains a leading cause of cancerassociated mortality worldwide [1,2,3]
MiR-346 is down-regulated in primary non‐small cell lung cancer (NSCLC) tissues and cell lines, and predicts a worse prognosis miR-346 expression was measured in 114 NSCLC samples and corresponding adjacent normal tissues by quantitative reverse transcription poly-merase chain reaction (qRT-PCR). miR-346 up-regulation was detected in 108/114 (94.74%) of NSCLC tumors (Fig. 1A)
Previous studies indicated that miR-346 might be an oncogenic miRNA in some cancers, including cervical cancer [21,22], cutaneous squamous cell carcinoma [23]
Summary
Non-small lung cancer (NSCLC) is responsible for over 80% of lung cancer-related deaths [4]. Despite of great improvements in chemotherapy and molecular-targeted treatment, the survival of this disease remains unsatisfactory. Tumor recurrence and metastasis are frequent and great challenges in the clinical treatment of NSCLC [4]. MicroRNAs (miRNAs) are a class of small, highly conserved, and non-coding RNAs that directly bind to target genes' 3'-UTRs (3'-untranslated regions) at some sequence-specific sites, which contribute to suppression of these genes expression [6,7]. Recent studies reveal that miRNAs leads to tumor proliferation, metastasis, apoptosis, stem cell maintenance, cell identity, and senescence [13,14,15,16,17,18]. Recent studies on miRNAs have brought mind-blowing insight into our knowledge of human tumors, there are still numerous of unknown details that need to be further elaborated
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